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. 2022 May 29;77(6):1600-1610.
doi: 10.1093/jac/dkac084.

Resistance mechanisms and molecular epidemiology of Pseudomonas aeruginosa strains from patients with bronchiectasis

Roberto Cabrera  1   2 , Laia Fernández-Barat  1   2 , Nil Vázquez  1   2 , Victoria Alcaraz-Serrano  1   2 , Leticia Bueno-Freire  1   2 , Rosanel Amaro  1   2 , Rubén López-Aladid  1   2 , Patricia Oscanoa  1   2 , Laura Muñoz  3 , Jordi Vila  3 , Antoni Torres  1   2
Affiliations

Resistance mechanisms and molecular epidemiology of Pseudomonas aeruginosa strains from patients with bronchiectasis

Roberto Cabrera et al. J Antimicrob Chemother. .

Abstract

Background: Non-cystic fibrosis bronchiectasis (BE) is a chronic structural lung condition that facilitates chronic colonization by different microorganisms and courses with recurrent respiratory infections and frequent exacerbations. One of the main pathogens involved in BE is Pseudomonas aeruginosa.

Objectives: To determine the molecular mechanisms of resistance and the molecular epidemiology of P. aeruginosa strains isolated from patients with BE.

Methods: A total of 43 strains of P. aeruginosa were isolated from the sputum of BE patients. Susceptibility to the following antimicrobials was analysed: ciprofloxacin, meropenem, imipenem, amikacin, tobramycin, aztreonam, piperacillin/tazobactam, ceftazidime, ceftazidime/avibactam, ceftolozane/tazobactam, cefepime and colistin. The resistance mechanisms present in each strain were assessed by PCR, sequencing and quantitative RT-PCR. Molecular epidemiology was determined by MLST. Phylogenetic analysis was carried out using the eBURST algorithm.

Results: High levels of resistance to ciprofloxacin (44.19%) were found. Mutations in the gyrA, gyrB, parC and parE genes were detected in ciprofloxacin-resistant P. aeruginosa strains. The number of mutated QRDR genes was related to increased MIC. Different β-lactamases were detected: blaOXA50, blaGES-2, blaIMI-2 and blaGIM-1. The aac(3)-Ia, aac(3)-Ic, aac(6″)-Ib and ant(2″)-Ia genes were associated with aminoglycoside-resistant strains. The gene expression analysis showed overproduction of the MexAB-OprM efflux system (46.5%) over the other efflux system. The most frequently detected clones were ST619, ST676, ST532 and ST109.

Conclusions: Resistance to first-line antimicrobials recommended in BE guidelines could threaten the treatment of BE and the eradication of P. aeruginosa, contributing to chronic infection.

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Figures

Figure 1.
Figure 1.
Antimicrobial susceptibility of all P. aeruginosa strains analysed by Etest. CIP, ciprofloxacin; IPM, imipenem; AMK, amikacin; TOB, tobramycin; ATM, aztreonam; MEM, meropenem; CAZ, ceftazidime; TZP, piperacillin/tazobactam; CST, colistin; CZA, ceftazidime/avibactam; C/T, ceftolozane/tazobactam; FEP, cefepime; R, resistant; I, intermediate; S susceptible.
Figure 2.
Figure 2.
Antimicrobial profile of all P. aeruginosa strains analysed. MR, moderately drug resistant; XDR, isolates resistant to all the antimicrobial agents except ≤2.
Figure 3.
Figure 3.
Number of resistant P. aeruginosa strains with each MIC value. CIP, ciprofloxacin; IPM, imipenem; AMK, amikacin; TOB, tobramycin; ATM, aztreonam; MEM, meropenem; CAZ, ceftazidime; TZP, piperacillin/tazobactam; CST, colistin; CZA, ceftazidime/avibactam; C/T, ceftolozane/tazobactam; FEP, cefepime.
Figure 4.
Figure 4.
Mutations detected in OprD, regulators of efflux systems and gene expression heat map for efflux pumps MexAB-OprM, MexCD-OprJ, MexEF-OprN and MexXY. MP, mutation pattern; NM, no mutation; _, absence. MP1 = D43N, S57E, S59R, E202Q, I210A, E230K, S240T, N262T, A267S, A281G, K296Q, Q301E, R310G, V359L, 372(V-DSSSSYAGL-)383. MP2 = K2E, D43N, S57E, S59R, E202Q, I210A, E230K, S240T, N262T, A267S, A281G, K296Q, Q301E, R310G, V359L, 372(V-DSSSSYAGL-)383. MP3 = K2E, T103S, K115T, F170L, E185Q, P186G, V189T, R310E, A315G. MP4 = S57E, S59R, V127L, E185Q, P186G, V189T, E202Q, I210A, E230K, S240T, N262T, T276A, A281G, K296Q, Q301E, R310E, A315G, L347M, 372(V-DSSSSYAGL-)383. MP5 = T103S, K115T, F170L, E185Q, P186G, V189T, R310E, A315G.
Figure 5.
Figure 5.
Genetic distance among the different STs. Hierarchical clustering of all STs found in P. aeruginosa strains, including alleles for the different housekeeping genes and CCs.
Figure 6.
Figure 6.
Minimum spanning tree of the 43 P. aeruginosa strains based on the MLST allelic profile and main CCs. Each circle represents a clone. The size of the circle corresponds to the number of isolates ascribed to that particular clone and each different colour inside the circle represents a different antimicrobial profile associated with each clone.
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